Dataset Information

Al-Tuwairqi2020 - Dynamics of cancer radiovirotherapy - Phase II treatment

ABSTRACT: This ordinary differential equation model of cancer radiovirotherapy dynamics is described in the publication: Salma M. Al-Tuwairqi, Najwa O. Al-Johani, Eman A. Simbawa, "Modeling dynamics of cancer radiovirotherapy", Journal of Theoretical Biology, Volume 506, 2020, 110405, ISSN 0022-5193, DOI: 10.1016/j.jtbi.2020.110405. Comment: This model is represented by the equations in system (14) of the publication manuscript and describes the cancer-virus interactions for the Phase II radiovirotherapy treatment. Abstract: Advances in genetic engineering have paved the way for a new therapy for cancer, which is called virotherapy. This treatment uses genetically engineered viruses which selectively infect, replicate in, and destroy cancer cells without damaging normal cells. Furthermore, current research and clinical trials have indicated that these viruses can be delivered as single agents or in combination with other therapies. In this paper, we propose systems of ordinary differential equations for modeling the dynamics of aggressive tumor growth under radiovirotherapy treatment. We divide the treatment period into two phases; consequently, we present two mathematical models. First, we formulate the virotherapy model as Phase I of the treatment. Then we extend the model to include radiotherapy in combination with virotherapy as Phase II of the treatment. Comprehensive qualitative analyses of both models are conducted. Furthermore, numerical experiments are performed in order to support the analytical results. An analysis of the parameters is also carried out to investigate their effects on the outcome of the treatment. Overall, the analytical results reveal that radiovirotherapy is more effective than, and a good alternative to, virotherapy, as it is capable of eradicating tumors completely.

DISEASE(S): Cancer

SUBMITTER: Rahuman Sheriff

PROVIDER: BIOMD0000001032 | BioModels | 2024-09-02

REPOSITORIES: BioModels

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	BIOMD0000001032?filename=Al-Tuwairqi2020%20-%20Fig8%20simulation.sedml	Other
	BIOMD0000001032?filename=Al-Tuwairqi2020%20-%20Phase%20II%20radiovirotherapy%20treatment-biopax2.owl	Owl
	BIOMD0000001032?filename=Al-Tuwairqi2020%20-%20Phase%20II%20radiovirotherapy%20treatment-biopax3.owl	Owl
	BIOMD0000001032?filename=Al-Tuwairqi2020%20-%20Phase%20II%20radiovirotherapy%20treatment-matlab.m	Other
	BIOMD0000001032?filename=Al-Tuwairqi2020%20-%20Phase%20II%20radiovirotherapy%20treatment-octave.m	Other

Items per page:

1 - 5 of 12

Publications

Modeling dynamics of cancer radiovirotherapy.

Al-Tuwairqi Salma M SM Al-Johani Najwa O NO Simbawa Eman A EA

Journal of theoretical biology 20200729

Advances in genetic engineering have paved the way for a new therapy for cancer, which is called virotherapy. This treatment uses genetically engineered viruses which selectively infect, replicate in, and destroy cancer cells without damaging normal cells. Furthermore, current research and clinical trials have indicated that these viruses can be delivered as single agents or in combination with other therapies. In this paper, we propose systems of ordinary differential equations for modeling the ...[more]

PMID: 32738266

Similar Datasets

Project description:Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines, however uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus, adenovirus, we have engineered a hepatocyte-safe wild type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this we have included binding sites for hepatocyte-selective microRNA122a within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of microRNA122a binding sites caused up to 80 fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild type Ad5 (5 x 1010 viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild type virus retained full activity within cancer cells and provides a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA-control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases. four groups which we had were: WT: RNA extracted from livers of mice treated with wild type Ad5, 3 Replicates miR: RNA extracted from livers of mice treated with wild type Ad5 bearing mir122-binding sites in the 3'UTR of E1A (3 Replicates) Luc: RNA extracted from livers of mice treated with non-replicating Ad5 (3 Replicates) PBS: RNA extracted from livers of mice treated with PBS only (3 Replicates)

Project description:The paper describes a model of oncolytic virotherapy. Created by COPASI 4.26 (Build 213) This model is described in the article: Mathematical Modelling of the Interaction Between Cancer Cells and an Oncolytic Virus: Insights into the Effects of Treatment Protocols Adrianne L. Jenner, Chae-Ok Yun, Peter S. Kim, Adelle C. F. Coster Bull Math Biol (2018) 80:1615–1629 Abstract: Oncolyticvirotherapyisanexperimentalcancertreatmentthatusesgenet- ically engineered viruses to target and kill cancer cells. One major limitation of this treatment is that virus particles are rapidly cleared by the immune system, preventing them from arriving at the tumour site. To improve virus survival and infectivity Kim et al. (Biomaterials 32(9):2314–2326, 2011) modified virus particles with the polymer polyethylene glycol (PEG) and the monoclonal antibody herceptin. Whilst PEG mod- ification appeared to improve plasma retention and initial infectivity, it also increased the virus particle arrival time. We derive a mathematical model that describes the inter- action between tumour cells and an oncolytic virus. We tune our model to represent the experimental data by Kim et al. (2011) and obtain optimised parameters. Our model provides a platform from which predictions may be made about the response of cancer growth to other treatment protocols beyond those in the experiments. Through model simulations, we find that the treatment protocol affects the outcome dramatically. We quantify the effects of dosage strategy as a function of tumour cell replication and tumour carrying capacity on the outcome of oncolytic virotherapy as a treatment. The relative significance of the modification of the virus and the crucial role it plays in optimising treatment efficacy are explored. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Occasional transmission of highly pathogenic avian H5N1 influenza viruses to humans causes severe pneumonia with high mortality. To better understand the mechanisms via which H5N1 viruses induce severe disease in humans, we infected cynomolgus macaques with six different H5N1 strains isolated from human patients and compared their pathogenicity and the global host responses to the virus infection. Although all H5N1 viruses replicated in the respiratory tract, there was substantial heterogeneity in their replicative ability and in the disease severity induced, which ranged from asymptomatic to fatal. A comparison of global gene expression between severe and mild disease cases indicated that interferon-induced up-regulation of genes related to innate immunity, apoptosis, and antigen processing/presentation in the early phase of infection was limited in severe disease cases, although interferon expression was up-regulated in both severe and mild cases. Furthermore, co-expression analysis of microarray data, which reveals the dynamics of host responses during the infection, demonstrated that the limited expression of these genes early in infection led to a failure to suppress virus replication and to the hyperinduction of genes related to immunity, inflammation, coagulation, and homeostasis in the late phase of infection, resulting in a more severe disease. Our data suggest that the attenuated interferon-induced activation of innate immunity, apoptosis, and antigen presentation in the early phase of H5N1 virus infection leads to subsequent severe disease outcome. Bronchial brushes for microarray studies were obtained from female cynomolgus macaques infected with influenza viruses. Three animals per group were inoculated with one of three H5N1 influenza viruses (VN3028II, VN30259 or VN3040). The early phase of infection refers to timepoints Pre (prior to infection), 1, and 3 days post-infection. The late phase of infection refers to days 5 and 7 post-infection. Samples collected prior to infection (labeled as Pre) served as control data for each infection group.